The proposed research will investigate how communication between brain cells directs nerve cell movement and growth, by studying these events in vitro using defined cell populations from cerebella of normal postnatal mice and those carrying the weaver mutation. The weaver mutation in the homozygous state results in the early death of the cerebellar granule cell neuron. It has been postulated that the neuronal death is due to an early block in axonal outgrowth and neuron migration caused by defective cell interactions. The properties and behavior of differentiating normal and weaver granule cells in vitro will be compared in order to determine how the mutant phenotype is expressed under cell culture conditions. Neuron survival, neurite initiation and elongation, cell migration and the presence of GM1 ganglioside, a developmentally regulated cell surface component, will be monitored. These studies will produce information concerning the dynamics of neuronal differentiation which cannot be obtained from anatomical studies of the normal or weaver mouse cerebellum. To determine whether the abnormal characteristics of weaver neurons are a result of defective cell-cell interactions during differentiation, normal or weaver neurons will be co-cultured with neurons or astroglia of different genotype and the properties of neuronal differentiation listed above will be monitored. In addition, conditioned medium, substrate attached material and cytoplasmic extracts will be tested for the presence of activities which alter the differentiation of normal or weaver granule cells.